Apparatus and method for characterization and treatment of tumors

ABSTRACT

Apparatus and methods are provided for performing an in situ characterization of a tissue mass which may be normal, malignant, or benign, and, based on the measured characteristics of the tissue mass, therapeutically treating the tissue mass to cause necrosis of the tissue. In an illustrative preferred embodiment, the characterization of the tissue is accomplished by measuring an electrical property of the tissue, such as electrical impedance, while treatment is accomplished by supplying heat to the tissue to induce cauterization.

RELATED APPLICATION DATA

This application is a continuation of application Ser. No. 08/398,644,filed Mar. 3, 1995, entitled APPARATUS AND METHOD FOR CHARACTERIZATIONAND TREATMENT OF TUMORS, now U.S. Pat. No. 5,630,426.

FIELD OF THE INVENTION

The present invention relates to apparatus and a method for performingin situ characterization of the cancerous nature of biological tissueand in situ necrosis of biological tissue.

BACKGROUND OF THE INVENTION

Apparatus and methods are known to identify, in situ, tumorous masses inbiological tissue by using the electrical properties of such tissue, forexample, by determination of electrical impedance or dielectricconstants. It is also known that some benign and malignant tumors may bedetermined from differences in the measured electrical properties ofsuch tissue.

It has been reported, for example, in T. Morimoto, et al., "Measurementof the Electrical Bio-Impedance of Breast Tumors," European SurgicalResearch, Vol. 22, pg. 86-92 (1990), that there are measurabledifferences between the electrical impedances of normal breast tissue,benign breast tumors, and malignant breast tumors. That paper describesa coaxial electrode arrangement wherein current pulses are conductedfrom an outer conductor of the electrode to a ground plate while voltagebetween an inner conductor of the electrode and the ground plate issensed to determine tissue impedance.

Apparatus and methods are also known for causing in situ necrosis oftumorous masses, such as by hyperthermia (raising the temperature ofbiological tissue through inductive, radiant, contact, and jouleanheating methods), the use of ionizing radiation (e.g., X-ray therapy),and cryosurgery. Several such devices are described in U.S. Pat. Nos.4,016,886 and 4,121,592 (hyperthermia); U.S. Pat. No. Re 34,421(ionizing radiation); and U.S. Pat. No. 4,140,109 (cryosurgery).

It is further known, for example by McRae U.S. Pat. No. 5,069,223, thatthe electrical impedance of an identified tissue mass may be measured todetermine the progress resulting from hyperthermic treatment. McRaedescribes an electrode-bearing probe that may be inserted intobiological tissue to sense the change in electrical impedance induced bya separate heating applicator.

A drawback of the above-described previously known apparatus and methodsis that a first device is used for characterizing the biological tissue(e.g., whether tissue is malignant or nonmalignant) and a second,separate, device is then required for treating the tissue. For example,the device described in the Morimoto reference may be used to identify atumorous tissue mass. The identified tissue mass may then be treated,for example, by hyperthermia, by positioning a treatment device at theproper location and actuating it. Finally, a method such as described inthe McRae patent may be used to sense the electrical impedance of thetissue exposed to hyperthermia to monitor the progress of thetherapeutic treatment.

Since the step of characterizing a target tissue is performedindependently of the step of positioning the treatment device, within oradjacent to that tissue, previously known apparatus and methods do notprovide accurate registration between the measuring device and thetreatment device. Consequently, the potential arises for incompletelytreating the intended tissue mass, thus leaving intact tumorous cells,or alternatively causing extensive necrosis to healthy tissue to avoidincomplete treatment. Moreover, these previously known techniques anddevices are excessively invasive and the sequential or combined natureof their use may result in significant patient discomfort.

In view of the foregoing, it would be desirable to provide apparatus andmethods in which a single instrument is used both to characterize and totreat tumors in situ. The ability to characterize and treat tumors witha single instrument would significantly reduce the invasiveness requiredin the characterization and treatment of tumors in accordance withpreviously known apparatus and methods.

It would also be desirable to provide apparatus and methods forconducting in situ characterization and treatment of tissue, using asingle device, to improve the efficiency of the medical procedure and toreduce patient distress during the medical procedure.

It would also be desirable to provide apparatus and methods for in situcharacterization and treatment of tissue that provides a high degree ofregistration between the measuring apparatus and the treatmentapparatus, thereby providing the ability to treat tissue adequatelywithout excessive damage to neighboring healthy tissue.

SUMMARY OF THE INVENTION

In view of the foregoing, it is an object of this invention to provide aapparatus and methods capable of both (1) characterizing, in situ,whether a tumor or tissue mass is normal, malignant, or nonmalignant and(2) inducing necrosis, in situ, of any tumor that is suspected to bemalignant.

It is another object of this invention to achieve both acharacterization of degree of malignancy and treatment of the tumor witha single instrument brought into direct contact with or adjacent to thetumor, thus improving the efficiency of the medical procedure andreducing patient distress during the medical procedure.

It is yet another object of the present invention to provide apparatusand methods for in situ characterization and treatment of suspectedmalignant tissue that provides a high degree of registration between themeasuring apparatus and the treatment apparatus, thereby providing theability to treat tissue adequately without excessive damage toneighboring healthy tissue.

It is a still further object of the present invention to provideapparatus and methods for causing tumor necrosis during a brief periodof time (e.g., several seconds to tens of seconds), where such apparatusand methods are compatible with existing noninvasive tumor-imagingtechniques.

These and other objects of the invention are accomplished in accordancewith the principles of the invention by providing apparatus and methodsfor in situ characterization and treatment of tumors that enables theuser both to measure one or more electromagnetic properties ofbiological tissue to characterize the degree of malignancy of the tumor(e.g., based on the vascularity of the tumor mass), and then to causenecrosis of biological tissue if it is determined that treatment isappropriate.

The apparatus of the present invention utilizes the measurabledifferences in one or more electromagnetic properties (e.g., electricalimpedance) of normal, malignant, and nonmalignant tissue to (1)discriminate, in situ, between malignant and nonmalignant tissue and (2)assess degree of malignancy, and (3) to treat, in situ, by inducingtumor necrosis through, e.g., inducing elevated temperatures in thetissue (i.e., cauterization or hyperthermia).

Further features of the invention, its nature and various advantageswill be more apparent from the accompanying drawings and the followingdetailed description of the preferred embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a first illustrative embodiment of themeasurement and treatment probe, control system, and connecting cable ofthe present invention;

FIG. 2 is a cross-sectional view of the measurement and treatment probeof FIG. 1, taken along the line 2--2 of FIG. 1;

FIG. 3 is a cross-sectional view of the measurement and treatment probeof FIG. 1, taken along line 4--4 of FIG. 1;

FIG. 4 is a side view of the measurement and treatment probe of FIG. 1,taken along the line 3--3, showing the probe inserted into biologicaltissue;

FIG. 5 is a perspective view of an alternative illustrative embodimentof the measurement and treatment probe, the control system, andconnecting cable of the present invention;

FIG. 6 is a top view of the measurement and treatment probe of FIG. 5,taken along line 6--6 of FIG. 5, showing the probe inserted intobiological tissue during the measurement mode of the apparatus;

FIG. 7 is an illustrative schematic diagram of an embodiment ofmeasurement and treatment circuitry constructed in accordance with thepresent invention;

FIG. 8 is an illustrative schematic diagram of an alternative embodimentof measurement and treatment circuitry constructed in accordance withthe present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates generally to apparatus having bothdiagnostic means, for characterizing whether a tissue mass is malignantor nonmalignant, and treatment means, for causing necrosis of the tissuemass if it is suspected of being malignant. In the exemplary embodimentof the apparatus and methods of the invention described hereafter,characterization of tumor type (e.g., either malignant or nonmalignant,as well as degree of virulence of malignancy based on vascularity) isbased on determining the electrical impedance, or resistance, ofbiological tissue, while necrosis of the biological tissue isillustratively accomplished by inducing elevated temperatures in thetissue.

It will of course be understood by those skilled in the relevant artsthat these exemplary embodiments of the invention in no way limit theintended use of the apparatus and methods of the present invention, andthat other characterizing parameters, such as dielectric constant, andother treatment modalities, such as cryogenic or ionizing radiation, mayalso be utilized within the scope and spirit of the present invention.

Referring to FIG. 1, a first illustrative embodiment of apparatus 10 ofthe present invention comprises measurement and treatment probe 20,cable 30 and controller 40.

Measurement and treatment probe 20 (hereinafter referred to as the"probe") has hand-engagable handle 21 at its proximal end and carriesboth diagnostic treatment means and therapeutic treatment means at itsdistal end 22. Distal portion 22 includes a plurality of electrodes foruse in the measurement of at least one electromagnetic property (e.g.,electrical impedance) of biological tissue and application of heatingcurrent to the target biological tissue, as described in detail below.

Probe 20 further includes shaft 23 removably coupled to handle 21 byconnector 24. Handle 21 may include manual measurement control 25 andmanual therapy control 26 for actuating the measurement and treatmentmodes of operation, respectively. Alternatively, handle 21 may include athree position slide or rocker-type switch instead of controls 25 and26, or these functions may be instead incorporated in a foot-pedal typeswitch.

Controller 40 is connected to handle 21 of probe 20 via cable 30. Cable30 includes the electrically conducting leads necessary for thetransmission of measurement signals, heating currents and switch controlsignals between probe 20 and controller 40. Controller 40 has circuitrythat energizes probe 20 during use in both diagnostic and therapeuticmodes of operation. Port 41 is provided on the faceplate of controller40 for accepting connector 31 of cable 30, while graduated dial or knob42 is provided to adjust the power level applied to probe 20. Controller40 connects to a conventional 110-120V 60 Hz power supply via plug 43and is turned on and off using switch 44.

Controller 40 also may include sensory display 45 to indicate a valueindicative of the measured electrical property (in diagnostic mode) oroutput voltage (in therapeutic mode). Sensory display 45 may be, e.g.,an audible indicator or a visual indicator such as a CRT or a recordingdevice. Sensory display 45 may also include an audible tone having afrequency (i.e., pitch) that corresponds to the value of the measuredelectrical property. The audible tone volume may be adjusted using dial46.

In a preferred embodiment of the apparatus of FIG. 1, the proximal endof cable 30 is removably connected to controller 40 using cableconnector 31, while the distal end of cable 30 may be removably coupledto, or integral with, probe handle 21. Cable 30 and handle 21 may beresterilized and reused multiple times. Alternatively, these componentsmay be formed of inexpensive, lightweight material (e.g., injectionmolded plastic) and therefore be completely disposable. Distal end 22and shaft 23 may also be disposable and may have a variety of lengths,diameters and electrode arrangements to accommodate a variety ofapplications as required by the physiological differences in the sizeand location of the tumor being characterized and treated.

Referring now to FIGS. 2 and 3, the construction of distal end 22 andhandle 21 of probe 20 of the first illustrative embodiment of thepresent invention is described. As shown in FIG. 2, distal end 22 ofprobe 20 includes a plurality of circumferential electrodes 51 through56 disposed on support member 50. Each electrode 51 through 56 iselectrically insulated from the others and from support member 50.Electrodes 51-56 comprise a suitable bio-inert material, for example,platinum, silver, gold or stainless steel, having a thickness in a rangeof 0.1 to 5.0 mils (0.002 to 0.13 mm). Electrodes 51-56 are spaced apartaxially along support member 50 at intervals which may vary according tothe intended application of probe 20.

Support member 23 may be constructed of a flexible or rigid electricallynonconductive material, or alternatively, may be constructed from ametallic tube (e.g., stainless steel Type 304) covered by a thinelectrically insulative coating, for example, a polymeric shrink tubing,or a thin layer of organic or inorganic electrically insulativematerial. Support element 50 of distal portion 22 may be insertedthrough bore 57 of shaft 23, thereby providing additional mechanicalsupport for support member 50. Support member 50 includes central bore58 for routing lead wires to each of electrodes 51-56.

Referring now also to FIG. 3, each electrode 51 through 56 is connectedto lead wire 61 through 66, respectively. Lead wires 61-66 areelectrically insulated from one another by a suitable electricallyinsulative coating, e.g., a polymeric covering. Each lead wire 61-66terminates in pins 71 through 76 electrically insulated from each otherin connector 24. Pins 71-76 engage contacts 81 through 86, respectively,disposed at the distal end of handle 21. Contacts 81-86 are electricallyconnected to lead wires 87 through 92, respectively, which extendthrough cable 30 and are coupled to controller 40 (see FIG. 1).Additional lead wires 93 through 96 allow the actuation of manualcontrols 25 and 26 on handle 21 to be detected by controller 40 toenergize the probe for either diagnostic or therapeutic modes ofoperation.

In a preferred embodiment of the illustrative apparatus of FIG. 1,support member 50 has a length and diameter suitable for allowing accessto tumors in the human body, such as breast tumors. By way of example,support member 50 of distal end 22 of probe 20 may have a diameter ofabout 1 mm and a length of 10 cm or longer. Tissue impedancemeasurements are conducted in the diagnostic mode of operation byconducting a low voltage radio-frequency current between outermostelectrodes 51 and 56, while electrode pairs 52, 53 and 54, 55 are usedto sense the voltage drop through the tissue along the length of supportmember 50, as described in detail below.

Once the tissue type has been characterized (e.g., by degree ofvascularity of the tumor), the tumor is treated by passing currentthrough electrode pair 52 and 53. Lead wires 62 and 63 are preferably ofa larger diameter (e.g., 0.1 to 0.25 mm) than lead wires 61 and 62-66because while lead wires 61 and 64-66 conduct only low voltages orcurrents used in the diagnostic mode, lead wires 62 and 63 carry bothlow voltages and currents during the diagnostic mode as well as highervoltages and currents during the therapeutic mode.

Operation of the apparatus of FIG. 1 is now described with respect toFIG. 4 and the methods of the present invention. As shown in FIG. 4,distal portion 22 of support member 23 is inserted into the patientpercutaneously so that distal portion 22 is positioned in closeproximity to (or within) tumor 201. Distal portion 22 may be guided tothe location of a targeted tissue mass using the coordinates, targetedtissue mass size and orientation determined in previous X-radiographic,sonographic, or other diagnostic imaging procedures.

Once distal portion 22 is properly positioned relative to the targetedtissue mass, manual measurement control 25 (see FIG. 3) is depressed toactivate measurement of an electromagnetic property of the targetedtissue mass and adjacent normal tissue. In particular, when manualmeasurement control 25 is depressed controller 40 applies a low voltage(e.g., less than about 10 volts) radio-frequency current (e.g., from 20kHz to 20 MHz) across the outermost pair of electrodes 51 and 56. Thiscurrent is indicated by flux lines 210 in FIG. 4. An indicationcorresponding to the measured electromagnetic property of the tissuemass, or a ratio of the measured tissue mass property to the measurednormal tissue property, is then provided, as described below.

The voltage applied between electrodes 51 and 56 for purposes ofmeasuring tissue impedance may be selected based upon several factors,including (1) the distance L₁ between electrodes 51 and 56, (2) theupper limit of the current level to maintain a desired maximum tissueheating (e.g., less than 2° C.), and (3) the lower limit of the currentlevel necessary to allow accurate measurement of the properties of thetumor 201 and the normal tissue 200 in region 203. Thus, the appliedradio-frequency voltage between electrodes 51 and 56 may typically beless than 10 volts and, more preferably, between 2 to 4 volts, and maybe controlled by a predetermined current limit set in controller 40. Theproperty measurements also may be made at several frequencies,preferably within the range 20 kHz to 20 MHz, to facilitatediscrimination of tissue type.

During the period of low level current flow between electrodes 51 and56, the voltage difference between electrode pairs 52 and 53 andelectrode pair 54 and 55 is measured by circuitry within controller 40,for example, voltmeter circuitry or a bridge circuit. By selecting theinterelectrode spacing L₃ between electrodes 52 and 53 to be the same asthe interelectrode spacing L₂ between electrodes 54 and 55 (see FIG. 4),the measured voltages between electrodes 52 and 53 and electrodes 54 and55 may be directly compared to assess the difference in electricalproperties in the two regions.

For example, the electrical impedance of tumor 201 and normal tissue 200in region 203 may be calculated based on (1) the measured currentflowing between electrodes 51 and 56, (2) the measured voltagedifference between electrode pairs 52/53 and 54/55, respectively, and(3) the interelectrode spacing L₂ and L₃ between these electrode pairs.Alternatively, the measured electrical property may be represented as aratio of the voltage differences between electrode pairs 52/53 and54/55.

If interelectrode spacings L₂ and L₃ are equal and the total electricalcurrent flowing through tissue adjacent to each of electrode pairs 52/53and 54/55 is also equal, the ratio of measured voltages betweenelectrode pairs 52/53 and 54/55 represents the ratio of electricalimpedance of tissue in the region of the tumor 201 and normal tissue 200in region 203, respectively. This measured ratio may be indicated bysensory display 45 of controller 40 (see FIG. 1).

If the operator then translates distal portion 22 forward and backwardin tissue 200, the displayed ratio and/or audible tone frequency ofsensory display 45 will vary, thus indicating the position of electrodes52 and 53 relative to tumor 201. Moreover, by comparing the parametervalue indicated on sensory display 45 to a table of predeterminedvalues, it is possible for the operator to characterize the tissue beingmeasured. This is accomplished, for example, by measuring the differencein electrical impedance between tissue known to be normal and tissuesuspected of being malignant.

Upon completing the assessment as to the malignancy of tumor 201, theoperator may either (1) withdraw distal portion 22 from the tissue or ifthe assessment indicates the tumor should be treated, (2) depress manualtherapy control 26 (see FIG. 3) until the desired thermal treatment(e.g, tissue cauterization) is accomplished. When therapy control 26 isdepressed controller 40 applies a sufficiently high radio-frequencyvoltage (e.g., 10-100 volts RMS between 100 kHz and 1 MHz, preferably350-500 kHz) across electrodes 52 and 53 to effect heating andcauterization of biological tissue located in the region 204 locatedbetween electrodes 52 and 53. In general, applicants expect that only afew seconds will be required to raise the temperature of the targetedtissue to a range of 60° C. to 100° C., thereby causing necrosis of thetissue. Once application of the treatment current has been completed,distal end 22 of probe 20 is withdrawn from the patient's tissue.

Optionally, a thermistor may be disposed on or within distal end 22, andin communication with temperature-sensing circuitry in controller 40, tomonitor the heating of the biological tissue in region 204. Preferably,the temperature of the biological tissue in region 204 is kept below atemperature at which the cauterization process causes the evolution ofsteam from the desiccating biological tissue, for example, less thanabout 100° C. Alternatively, probe 20 may include means for venting anyvapors produced by heating of the biological tissue.

Referring now to FIG. 5, a second illustrative embodiment of apparatus100 of the present invention is described. Like components of apparatus100 are designated with like numbers as apparatus 10 of FIG. 1. Thus,for example, cable 30 and controller 40 of the system of FIG. 5 areessentially the same as described above with respect to FIG. 1, exceptthat diagnostic and therapeutic modes of operation are activated byfootpedal 48 coupled to controller 40 via cable 47.

Apparatus 100 may provide certain advantages relative to thefirst-described embodiment in that it includes two measurement andtreatment probes 100, which may be inserted into normal biologicaltissue adjacent to a suspected tumorous region. Apparatus thereforeprovides the capability to characterize the suspected tumor, withoutcreating a risk of seeding the needle track with cancerous cells, ascould conceivably occur with the single probe design of the firstembodiment.

Measurement and treatment probes 110 of apparatus 100 are coupled tocable 30 via connector 32. Measurement and treatment probes 110(hereinafter, the "probes") are identical and similar in design tomeasurement and treatment probe 20, described above. Each of probes 110includes a hand-engagable body 111, and a removably connected supportmember 112. Support members 112 are similar in design and constructionto support member 50 described above with respect to FIG. 2. Distalportions 113 of support members 112 carry two or more electrodes for usein the measurement of an electromagnetic property (e.g., electricalimpedance) and application of heating current to the biological tissue.

Probes 110 are connected to controller 40 via cable 30. Cable 30 isdivided into two (or more) cable branches 33 distally of connector 32 toprovide connection to handles 111. Cable 30 includes the conductingleads necessary for the transmission of measurement signals and heatingcurrents between controller 40 and probes 110, and may include suitableconnectors at its ends so that cable 30 may be resterilized and reusedmultiple times.

Referring now to FIG. 6, probes 110 of the second illustrativeembodiment are described in greater detail. Similar to probe 20described above, probes 110 may have support members 112, removablyconnected to handles 111, and may be disposable. Support members 112have lengths and diameters suitable for allowing access to tumors in thehuman body, for example, diameters of about 1 mm and lengths of 10 cm orlonger. Support members 111 may be connected by bridge 114 so that theylie in a common plane. Bridge 114 may have an adjustable length L₄between support members 112.

Electrodes 115 and 116 are positioned along distal portions 113 of eachof support members 112. During diagnostic operation of apparatus 100, anelectromagnetic property of tissue in region 205 (e.g., electricalimpedance) is measured by passing a sense current from electrode 115 ofa first probe 110 to electrode 115 of a second probe 110, while anelectromagnetic property of tissue in region 206 is measured by passinga sense current through electrodes 116 of the respective probes 110.These sense currents are illustrated by flux lines 211 and 212,respectively, in FIG. 6.

As for probe 20 described above, the voltage and current passed throughtissue in regions 205 and 206 during the diagnostic mode is sufficientlylow to prevent any significant heating of tissue located between theelectrode pairs 115 and 116 (e.g., voltage generally less than 10 voltsat frequencies between 20 kHz and 10 MHz). During a therapeutic mode ofoperation of apparatus 100, higher voltages and currents are supplied toelectrodes 115 of the first and second probes 110, thereby causingcauterization of tissue in region 205, including the tumor 207.

Operation of the apparatus of FIGS. 5 and 6 is accomplished usingfootpedals 49a and 49b. In particular., footpedal 49a replaces manualmeasurement control 25 of probe 20 (see FIG. 1) and is used to activatethe diagnostic mode of operation of apparatus 100, while footpedal 49breplaces manual therapy control 26 during the therapeutic mode ofoperation.

During a diagnostic mode of operation, distal ends 113 of probes 110 areinserted into the patient percutaneously and in close proximity withtumor 207. As described above, this insertion step may be guided usingcoordinates, tumor size and orientation determined in previousX-radiographic, sonographic and/or other diagnostic imaging procedures.Footpedal 49a is depressed to activate measurement of theelectromagnetic property of tumor 207 in region 205 and of adjacentnormal tissue in region 206. As described with respect to the embodimentof FIG. 1, an indication of either a measured value of anelectromagnetic property or a ratio of such properties is provided bysensory display 45 to enable the characterization of the suspected tumor207 allowing the user to address whether tumor 207 is appropriate fortreatment.

The operator then releases footpedal 49a and withdraws probes 110 fromthe patient's tissue or, if the assessment indicates the suspected tumor207 should be treated, depresses footpedal 49b until the desired tissuetreatment (e.g., cauterization) is accomplished. The duration of theapplication of heating current to the biological tissue in region 205may be selected based on a number of factors, for example, a measuredperiod of time or level of current flowing between electrodes 115 for agiven applied voltage. Probes 110 may be withdrawn when application ofthe therapeutic current has been completed. Alternatively, thediagnostic mode of operation may be repeated following application ofthe therapeutic current to assess the degree of necrosis induced in thetissue.

Applicants expect that heating of tissue 200 and tumor 207 in region 205will cause not only the desired cauterization of tissue in region 205,but will also cause an increase in the electrical impedance of tissue inregion 205. Thus, for a fixed (constant) level of applied voltagebetween electrodes 115, the level of electrical current flowing willdecay as the cauterization of tissue 200 and tumor 207 proceeds.Applicants therefore expect that adequate cauterization of the tissue inregion 205 will result in the electrical current level falling to a lowand relatively constant value, at which time application of heatingpower to the tissue may be terminated.

Thus, in addition to the use of a thermistor to determine completenessof cauterization as described with reference to the embodiment of FIG.1, applicants expect that another method of making this determinationmay involve monitoring the above-described fall off in electricalcurrent supplied to probes 110 during the therapeutic mode of operation.For example, the decay of the electrical current level and theattainment of an adequate thermal treatment may be represented by anaudible tone having a frequency (pitch) indicative of the level of theelectrical current flowing between electrodes 115.

Referring now to FIGS. 7 and 8, embodiments of controller 40 of thepresent invention are described for use with apparatus 10 and 100. Inaccordance with the illustrative embodiments of apparatus 10 and 100described hereinabove, in which an electrical property of the tissue ismeasured followed by inducing cauterization of the tissue by passingelectric current through it, controller 40 includes both circuitry formeasuring at least one electromagnetic property of biological tissueduring a diagnostic mode of operation and circuitry for generating aradio-frequency voltage during a therapeutic mode of operation. Whilecircuitries for performing these functions individually are per seknown, illustrative arrangements suitable for use with apparatus 10 and100 of the present invention are provided.

FIG. 7 shows a first illustrative embodiment of controller 40 (incombination with electrodes as in apparatus 100) including constantlow-current power supply 120, adjustable voltage level power supply 121,sense circuitry 122, display circuitry 123, and switching circuitry 124.Constant low-current power supply 120 supplies a low voltage (less than10 volts RMS) constant low current to electrodes 115 and 116 ofapparatus 100 during the diagnostic mode of operation of apparatus 100,such that tissue 200 in the vicinity of electrodes 115 and 116preferably experiences no ore than a 2-4° C. increase in temperature.Power supply 120 may operate at a single radio-frequency in the range 20kHz to 10 MHz, or to account for inductance and capacitance effects ofthe tissue, may sample the electromagnetic property of the tissue at anumber of different frequencies within that range.

Sense circuitry 122 measures the resulting voltage differences betweeneach of electrode pair 115 and electrode pair 116, using for example,voltmeter circuitry 125 or bridge circuitry. If the measurement isperformed at multiple frequencies, suitable averaging circuitry may alsobe employed for processing the samples. A ratio of the measured voltagesmay then be computed and displayed by display circuitry 123 usingsuitable analog or digital circuitry.

Once the operator has assessed the measured values during the diagnosticmode of operation, the operator may then actuate apparatus 100 to entera therapeutic mode of operation, for example, by depressing footpedal49b (see FIG. 5). Actuation of the therapeutic mode causes switchingcircuitry 124 to couple electrode pair 115 to adjustable voltage levelpower supply 121 via contacts 126, while electrode pair 116 isopen-circuited.

Power supply 121 provides a radio-frequency voltage (e.g., 10-100 voltsRMS at between 100 kHz and 1 MHz, and preferably 200-500 kHz) toelectrodes 115 for a suitable time period, for example; 10 seconds, tocause adequate necrosis of target tissue 207. The output voltage ofpower supply 121 is preferably independent of the load impedance. Asdescribed above, the operator may then move between diagnostic andtherapeutic modes of operation of apparatus 100 to evaluate or monitorthe progress of the tissue treatment (i.e., cauterization of thetissue).

Referring to FIG. 8, an alternative embodiment of controller 40 (incombination with electrodes as in apparatus 100) of the presentinvention is described. Controller 40 of FIG. 8 includes constantlow-voltage power supply 130, adjustable voltage level power supply 131,sense circuitry 132, display circuitry 133, and switching circuitry 134.Constant low-voltage power supply 130 supplies a constant low voltage(less than 10 volts RMS), low level current to electrodes 115 and 116 ofapparatus 100 during the diagnostic mode of operation of apparatus 100.

As for the embodiment of FIG. 7, the power supplied by power supply 130is such that tissue 200 in the vicinity of electrodes 115 and 116preferably experiences no more than a 2-4° C. increase in temperature.Power supply 130 may operate at a single radio-frequency in the range 20kHz to 10 MHz, or sweep through that range to sample the tissue propertyat multiple frequencies.

Sense circuitry 132 measures the resulting current levels between eachof electrode pair 115 and electrode pair 116 using, for example,suitable current meter circuitry 135. If the measurement is performed atmultiple frequencies, suitable averaging circuitry may also be employedfor processing the samples. A ratio of the measured currents may then becomputed and displayed by display circuitry 133 using suitable analog ordigital circuitry. This embodiment may yield more accurate tissueimpedance measurements then the embodiment of FIG. 7 since the currentsignals conducted between electrode pairs 115 and 116 may be lesssensitive to tissue inductance and capacitance.

Power supply 131 and switching circuitry 134 may then be actuated by theoperator's causing apparatus 100 to enter a therapeutic mode ofoperation, for example, by depressing footpedal 49b. Actuation of thetherapeutic mode causes switching circuitry 134 to couple electrode pair115 to adjustable voltage level power supply 131 via contacts 136, whileelectrode pair 115 is open-circuited. Power supply 121 then operates toprovides a suitable radio-frequency voltage to electrodes 115, asdescribed above, to cause adequate necrosis of target tissue 207.Isolation transformers 138 may also be provided to ensure that nolow-frequency leakage currents are conducted to tissue 200.

Alternatively, circuitry for measuring the electrical impedance ofbiological tissue as described, for example, in the above-mentionedMorimoto reference and U.S. Pat. No. 5,069,223, or circuitry formeasuring the dielectric constants of biological tissue, such as found,for example, in U.S. Pat. Nos. 4,458,694 and 4,291,708, may be used incontroller 40. Treatment circuitry for heating of biological tissue,such as is described, for example, in U.S. Pat. Nos. 4,016,886 and4,121,592 may also be employed.

Illustrative embodiments 10 and 100 of the present invention provide asignificant advantage over previously known measurement and treatmentdevices by providing both diagnostic and therapeutic capabilities in asingle instrument. In particular, because the electrodes used forsensing the properties of the tumor during the diagnostic mode andtreating the tumor during the therapeutic mode are located at knowndistances along the probes 20 and 110 (and in some cases are the sameelectrodes), the operator can achieve precise registration of theelectrodes relative to the tumor during these two modes of operation.Such precise registration would be unachievable with previously knowninstruments, where a first measuring instrument and a second treatmentinstrument are required.

A further advantage of the probe of the present invention relates to theability to iterate between treatment and measuring modes of operation.Thus, for example, a operator may be able to treat several tissueregions through a single incision in a serial manner, operating theinstrument in diagnostic mode and then in therapeutic mode at firstlocation in the patient's tissue. Following treatment at the firstlocation, the operator may then move probe 20 (or probes 110) to a newposition and repeat the procedure. Alternatively, even after havingperformed partial cauterization of a tumor, the operator might choose tomeasure the electrical property for a treated region to confirm theextent of the tissue treatment, followed by resumed treatment, thusalternating between diagnostic and treatment modes at a single location.

Applicants also contemplate that the electrical impedance of the tissue,or other property, be measured at two or more radio-frequencies toprovide additional data for use in assessing the malignancy of a tumor.In an alternative embodiment of the present invention, apparatus 10 and100 may be used to measure the dielectric constant of biological tissueto differentiate between malignant and nonmalignant tumors, assessdegree of malignancy, or differentiate between tumors and normal tissuerather than electrical impedance.

In yet another embodiment, therapeutic treatment of a tumor suspected tobe malignant using measurement apparatus and methods described above mayalternatively or additionally include the use of ionizing radiation suchas the miniature X-ray therapy apparatus described in U.S. Pat. No. Re34,421. As yet a further alternative, tumor necrosis may be achieved byexposing the targeted tissue to cryogenic temperatures, for example, asdescribed in U.S. Pat. No. 4,140,109.

While preferred illustrative embodiments of the present invention aredescribed above, it will be obvious to one skilled in the art thatvarious changes and modifications may be made therein without departingfrom the invention and it is intended in the appended claims to coverall such changes and modifications which fall within the true spirit andscope of the invention.

What is claimed is:
 1. Apparatus for in situ diagnosis of biologicaltissue comprising:an RF generator that outputs an alternating currentvoltage waveform; a probe coupled to the RF generator, the probecomprising an elongate member including first and second electrodesdisposed on the elongate member, the second electrode spaced apart fromthe first electrode, the probe having a first mode of operation in whichthe first electrode senses a first value of a parameter indicative of aproperty of a biological tissue for a first region of tissue adjacent tothe first electrode, and the second electrode senses a second value ofthe parameter for a second region of tissue adjacent to the secondelectrode; first circuitry coupled to the first and second electrodesfor sensing the first and second values during the first mode ofoperation, and for comparing the first and second values to enabledifferentiation of the tissue in the second region from among normalbiological tissue, malignant tumorous biological tissue, andnonmalignant tumorous biological tissue; and means for coupling theprobe to the first circuitry and the RF generator.
 2. Apparatus asdefined in claim 1 wherein the probe further comprises a selectablesecond mode of operation causing in situ necrosis of the biologicaltissue, the probe further comprising:second circuitry coupled to thesecond electrode for inducing necrosis of the biological tissue in thesecond region during the second mode of operation; and means forcoupling the probe to the second circuitry.
 3. Apparatus as defined inclaim 2 wherein the elongate member further comprises a third electrodeinterposed between the first and second electrodes.
 4. Apparatus asdefined in claim 2 wherein the probe further comprises a switch forselectively activating the first and second modes of operation. 5.Apparatus as defined in claim 2 wherein the second circuitry inducesnecrosis of the biological tissue by supplying a voltage to the secondelectrode.
 6. Apparatus as defined in claim 1 further comprising:a userinterface for providing a sensory indication responsive to an output ofthe first circuitry.
 7. Apparatus as defined in claim 6 wherein the userinterface provides a sensory indication corresponding to a degree ofvascularity of the biological tissue in the second region to enablecharacterization of the degree of malignancy.
 8. Apparatus as defined inclaim 7, wherein the user interface comprises a visual display or anauditory device.
 9. Apparatus as defined in claim 1, wherein theparameter indicative of a property of the biological tissue is selectedfrom the group consisting of electrical impedance and dielectricconstant.
 10. Apparatus as defined in claim 1, wherein the firstelectrode comprises a material selected from the group consisting ofplatinum, silver, gold, stainless steel, or other biocompatibleelectrically conductive materials.
 11. A method for in situ diagnosis ofbiological tissue comprising steps of:inserting a probe having first andsecond spaced apart electrodes in a biological tissue in situ; applyingan RF voltage to the biological tissue; sensing a first value of aparameter indicative of a property of the biological tissue for a firstregion of tissue adjacent to the first electrode; sensing a second valueof the parameter for a second region of tissue adjacent to the secondelectrode; comparing the first and second values to differentiate thetissue in the second region among normal biological tissue, malignanttumorous biological tissue, and nonmalignant tumorous biological tissue;and characterizing the tissue in the second region based upon a resultof comparing the first and second values.
 12. The method as defined inclaim 11 further including a step of in situ treatment of the biologicaltissue comprising:selectively actuating the probe to cause necrosis ofthe second region of biological tissue.
 13. The method of claim 12,wherein the step of selectively actuating the probe to cause necrosisinduces elevated temperatures in the second region of biological tissue.14. The method of claim 13, wherein the elevated temperatures are in arange of 60° C. to 100° C.
 15. The method of claim 11 wherein the stepof characterizing comprises assessing the degree of malignancy of thesecond region.
 16. The method of claim 11, wherein the parameter isselected from a group consisting of electrical impedance and dielectricconstant.
 17. The method of claim 16, wherein the step of sensingmeasures the electrical impedance of the biological tissue at one ormore frequencies in the range of 20 kHz to 20 MHz.
 18. An apparatus foruse with an RF generator for in situ diagnosis of biological tissuecomprising:a handle; a support member removably connected to the handle;first and second electrodes disposed on the support member inspaced-apart relation, the first and second electrodes adapted to becoupled to an RF generator, the first electrode sensing a first value ofa parameter indicative of a property of a biological tissue for a firstregion of tissue adjacent to the first electrode, and the secondelectrode for sensing a second value of the parameter for a secondregion of tissue adjacent to the second electrode; and circuitry coupledto the first and second electrodes for sensing the first and secondvalues, and for comparing the first and second values to enabledifferentiation of the tissue in the second region from among normalbiological tissue, benign tumorous biological tissue, and malignanttumorous biological tissue.
 19. The probe as defined in claim 18 furthercomprising means, disposed from the support member, for causing in situnecrosis of the biological tissue in the second region.
 20. A probe asdefined in claim 19 further comprising a switch, operatively coupled tothe second electrode and the means for causing in situ necrosis, theswitch selectively activating the second electrode for sensing or themeans for causing in situ necrosis.
 21. Apparatus as defined in claim 18further comprising a user interface to provide a sensory indicationcorresponding to a degree of vascularity of the biological tissue in thesecond region to enable characterization of the degree of malignancy.22. A probe as defined in claim 18, wherein the first and secondelectrodes comprises a material selected from the group consisting ofplatinum, silver, gold, stainless steel, and other biocompatibleelectrically conductive materials.